| 1. |
- Bernberg, Evelina, 1981, et al.
(författare)
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Effects of social isolation and environmental enrichment on atherosclerosis in ApoE-/- mice
- 2008
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Ingår i: Stress. - 1607-8888 .- 1025-3890. ; 11:5, s. 381-9
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Tidskriftsartikel (refereegranskat)abstract
- Social support and a stimulating environment have been suggested to reduce stress reactions and cardiovascular risk. The aim of this study was to assess the role of environmental enrichment and social interaction for development of atherosclerosis in atherosclerosis prone mice. Male ApoE-/- mice were divided into four groups and followed during 20 weeks: (i) enriched environment (E, n=12), (ii) deprived environment (ED, n=12), (iii) enriched environment with exercise (E-Ex, n=12) and (iv) socially deprived by individual housing (SD, n=10). Plasma lipid and cytokine concentrations were measured. Atherosclerosis was quantified in cross-sections of innominate artery and en face in thoracic aorta. Plaque area was significantly increased in SD mice in the innominate artery (P<0.05 vs. all other groups), but not in the thoracic aorta. Plasma lipids were increased in SD mice (P<0.001 vs. all for total cholesterol, P<0.05 vs. E and P<0.01 vs. ED for triglycerides). Plasma concentration of granulocyte-colony stimulating factor (G-CSF) was decreased in SD mice compared to E mice (P<0.05). Thus, social isolation increased atherosclerosis and plasma lipids in ApoE-/- mice. Reduction in plasma G-CSF levels may hamper endothelial regeneration in the atherosclerotic process. While environmental enrichment did not affect atherosclerosis, social isolation accelerated atherosclerosis.
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| 2. |
- Hägg Samuelsson, Ulrika, 1973, et al.
(författare)
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Gene expression profile and aortic vessel distensibility in voluntarily exercised spontaneously hypertensive rats: potential role of heat shock proteins
- 2005
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Ingår i: Physiol Genomics. - 1531-2267 .- 1094-8341. ; 22:3, s. 319-26
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Tidskriftsartikel (refereegranskat)abstract
- Physical exercise is considered to be beneficial for cardiovascular health. Nevertheless, the underlying specific molecular mechanisms still remain unexplored. In this study, we aimed to investigate the effects of voluntary exercise on vascular mechanical properties and gene regulation patterns in spontaneously hypertensive rats. By using ultrasound biomicroscopy in an ex vivo perfusion chamber, we studied the distensibility of the thoracic aorta. Furthermore, exercise-induced gene regulation was studied in aortae, using microarray analysis and validated with real-time PCR. We found that distensibility was significantly improved in aortas from exercising compared with control rats (P < 0.0001). Exercising rats demonstrated a striking pattern of coordinated downregulation of genes belonging to the heat shock protein family. In conclusion, voluntary exercise leads to improved vessel wall distensibility and reduced gene expression of heat shock protein 60 and 70, which may indicate decreased oxidative stress in the aortic vascular wall.
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| 3. |
- Naylor, Andrew Stuart, 1977, et al.
(författare)
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Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain.
- 2008
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 105:38, s. 14632-7
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Tidskriftsartikel (refereegranskat)abstract
- Cranial radiation therapy is commonly used in the treatment of childhood cancers. It is associated with cognitive impairments tentatively linked to the hippocampus, a neurogenic region of the brain important in memory function and learning. Hippocampal neurogenesis is positively regulated by voluntary exercise, which is also known to improve hippocampal-dependent cognitive functions. In this work, we irradiated the brains of C57/BL6 mice on postnatal day 9 and evaluated both the acute effects of irradiation and the effects of voluntary running on hippocampal neurogenesis and behavior 3 months after irradiation. Voluntary running significantly restored precursor cell and neurogenesis levels after a clinically relevant, moderate dose of irradiation. We also found that irradiation perturbed the structural integration of immature neurons in the hippocampus and that this was reversed by voluntary exercise. Furthermore, irradiation-induced behavior alterations observed in the open-field test were ameliorated. Together, these results clearly demonstrate the usefulness of physical exercise for functional and structural recovery from radiation-induced injury to the juvenile brain, and they suggest that exercise should be evaluated in rehabilitation therapy of childhood cancer survivors.
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| 4. |
- Dean, Justin M, et al.
(författare)
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Partial neuroprotection with low-dose infusion of the alpha2-adrenergic receptor agonist clonidine after severe hypoxia in preterm fetal sheep.
- 2008
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Ingår i: Neuropharmacology. - : Elsevier BV. - 0028-3908. ; 55:2, s. 166-74
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that brief alpha(2)-adrenergic receptor blockade increased neuronal injury after severe hypoxia in preterm fetal sheep. We now examine whether infusion of an alpha(2)-adrenergic receptor agonist, clonidine, is neuroprotective. Preterm fetal sheep (70% gestation) received either saline-vehicle or clonidine at either 10 microg/kg/h (low-dose) or 100 microg/kg/h (high-dose) from 15 min until 4 h after 25 min of umbilical cord occlusion. Both low- and high-dose clonidine infusions after sham-occlusion were associated with transient EEG suppression but no neuronal loss. Low-dose but not high-dose clonidine infusions after umbilical cord occlusion were associated with a significant overall increase in numbers of surviving neurons after three days' recovery. High-dose clonidine was associated with transient hyperglycemia and increased numbers of delayed electrographic seizures. These results provide further evidence that alpha(2)-adrenergic receptor activation shortly after perinatal hypoxia-ischemia can promote neural recovery, but highlight the complex dose-response of exogenous therapy.
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| 5. |
- Hägg Samuelsson, Ulrika, 1973, et al.
(författare)
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Voluntary physical exercise-induced vascular effects in spontaneously hypertensive rats
- 2004
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Ingår i: Clin Sci (Lond). - 0143-5221. ; 107:6, s. 571-81
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Tidskriftsartikel (refereegranskat)abstract
- Forced training has been shown to have beneficial vascular effects in various animal exercise models. In the present study, we explored possible physiological and molecular effects of voluntary physical exercise on various vascular beds. SHR (spontaneously hypertensive rats) performed voluntary exercise for 5 weeks in a computerized wheel cage facility. Ex vivo myograph studies revealed an increased sensitivity of the ACh (acetylcholine)-mediated vasodilation in resistance arteries of the exercised animals (ED50=15.0+/-3.5 nmol/l) compared with the controls (ED50=37.0+/-8.8 nmol/l; P=0.05). The exercise/control difference was abolished after scavenging reactive oxygen radicals. In conduit arteries, ACh induced a similar vasodilatory response in both groups. The in vivo aortic wall stiffness, assessed by means of Doppler tissue echography, was significantly lower in the exercising animals than in controls. This was demonstrated by significantly increased peak systolic aortic wall velocity (P=0.03) and the velocity time integral (P=0.01) in exercising animals compared with controls. The relative gene expression of eNOS (endothelial nitric oxide synthase) was similar in both groups of animals, whereas Cu/ZnSOD (copper/zinc superoxide dismutase) gene expression was significantly increased (+111%; P=0.0007) in the exercising animal compared with controls. In conclusion, voluntary physical exercise differentially improves vascular function in various vascular beds. Increased vascular compliance and antioxidative capacity may contribute to the atheroprotective effects associated with physical exercise in conduit vessels.
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| 6. |
- Järlestedt, Katarina, et al.
(författare)
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Decreased survival of newborn neurons in the dorsal hippocampus after neonatal LPS exposure in mice.
- 2013
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Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 253, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- Experimental studies show that inflammation reduces the regenerative capacity in the adult brain. Less is known about how early postnatal inflammation affects neurogenesis, stem cell proliferation, cell survival and learning and memory in young adulthood. In this study we examined if an early life inflammatory challenge alters cell proliferation and survival in distinct anatomical regions of the hippocampus and whether learning and memory were affected. Lipopolysaccharide (LPS, 1 mg/kg) was administered to mice on postnatal day (P) 9 and proliferation and survival of hippocampal cells born either prior to (24 h before LPS), or during the inflammatory insult (48h after LPS) was evaluated. Long-term cell survival of neurons and astrocytes was determined on P 41 and P 60 in the dorsal and ventral horns of the hippocampus. On day 50 the mice were tested in the trace fear conditioning paradigm.There was no effect on the survival of neurons and astrocytes that were born before LPS injection. In contrast, the number of neurons and astrocytes that were born after LPS injection were reduced on P 41. The LPS-induced reduction in cell numbers was specific for the dorsal hippocampus. Neither early (48 h after LPS) or late (33 days after LPS) proliferation of cells was affected by neonatal inflammation and neonatal LPS did not alter the behaviour of young adult mice in the trace fear conditioning test.These data highlight that neonatal inflammation specifically affects survival of dividing neurons and astrocytes, but not post-mitotic cells. The reduction in cell survival could be attributed to less cell survival in the dorsal hippocampus, but had no effect on learning and memory in the young adult.
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| 7. |
- Lindholm, Catharina, 1967, et al.
(författare)
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Mucosal vaccination increases endothelial expression of mucosal addressin cell adhesion molecule 1 in the human gastrointestinal tract.
- 2004
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Ingår i: Infection and immunity. - 0019-9567. ; 72:2, s. 1004-9
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Forskningsöversikt (refereegranskat)abstract
- Homing of leukocytes to various tissues is dependent on the interaction between homing receptors on leukocytes and their ligands, addressins, on endothelial cells. Mucosal immunization results in homing of antigen-specific lymphocytes back to the mucosa where they first encountered the antigen. However, it is unknown whether this homing of antigen-specific cells is mediated by an altered endothelial addressin expression after vaccination. Using different immunization routes with an oral cholera vaccine, we show that the endothelial expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) is increased in the gastric and upper small intestinal mucosae after immunization through various local routes in the upper gastrointestinal tract. In contrast, rectal immunization did not influence the levels of MAdCAM-1 in the gastric or duodenal mucosa. Furthermore, we show that MAdCAM-1 can be induced on human endothelial cells by tumor necrosis factor alpha (TNF-alpha) and gamma interferon. The vaccine component cholera toxin B subunit (CTB) increased MAdCAM-1 expression on endothelial cells in cultured human gastric explants, an effect that seemed to be mediated by TNF-alpha. In conclusion, MAdCAM-1 expression is increased in the upper gastrointestinal tract after local immunizations with a vaccine containing CTB. This strongly suggests the involvement of MAdCAM-1 in the preferential homing of mucosal lymphocytes to their original site of activation.
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| 8. |
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| 9. |
- Manni, Luigi, 1962, et al.
(författare)
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Effect of exercise on ovarian morphology and expression of nerve growth factor and alpha(1)- and beta(2)-adrenergic receptors in rats with steroid-induced polycystic ovaries
- 2005
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Ingår i: J Neuroendocrinol. ; 17:12, s. 846-58
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Tidskriftsartikel (refereegranskat)abstract
- Oestadiol valerate (EV)-induced polycystic ovaries (PCO) in rats cause anovulation and cystic ovarian morphology. Denervation of ovarian sympathetic nerves restores ovulatory disruption. In the present study, we determined whether 5 weeks of voluntary exercise influence ovarian morphology and the expression of sympathetic markers in the EV-induced PCO rat model. The effect of exercise on (i) ovarian morphology; (ii) mRNA and protein expression of nerve growth factor (NGF); and (iii) mRNA and number of ovarian-expressing cells for the NGF receptor (p75 neurotrophin receptor) and the alpha(1a)-, alpha(1b)-, alpha(1d)- and beta(2)-adrenergic receptors (ARs) in rats with EV-induced PCO was evaluated. PCO was induced by a single i.m. injection of EV, and controls were injected with oil alone in adult cycling rats. The rats were divided into four groups: (i) control (oil); (ii) exercise group (oil + exercise); (iii) a PCO group (EV); and (iv) a PCO exercise group (EV + exercise). The exercise and PCO exercise groups ran voluntarily for 5 weeks in computer-monitored wheels placed in the cages where they were housed. The results obtained indicated that ovarian morphology was almost normalised in the PCO exercise group; NGF mRNA and protein concentrations were normalised in the PCO exercise group; high numbers of NGF receptor expressing cells in PCO ovaries were lowered by exercise; and the number of immunopositive cells of the different AR subtypes were all reduced after exercise in the PCO group, except for the alpha(1b)- and beta(2)-AR whereas the mRNA levels were unaffected, indicating transcriptional regulation. In conclusion, our data indicate a beneficial effect of regular exercise, as a modulator of ovarian sympathetic innervation, in the prevention and treatment of human PCOS.
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| 10. |
- Naylor, Andrew Stuart, 1977
(författare)
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Differential effects of voluntary running on hippocampal plasticity in the adult rat brain
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The continuation of neuronal birth from dividing neural stem cells in the dentate gyrus of the hippocampus throughout adulthood is known to play an important role in maintaining normal hippocampal function, such as memory and learning. Negative alterations in the levels of adult neurogenesis have also been linked to several neurodegenerative diseases, including Alzheimer s disease and mood disorders such as depression. This thesis investigated the effects of varying durations of voluntary running on the proliferation and differentiation of newborn cells in the hippocampus and the regulatory mechanisms involved in running induced hippocampal plasticity in adult rats. Animals were allowed free access to running wheels for 9, 24 or 43 days. On the last two days of voluntary running, bromodeoxyuridine was administered to label new cells and then the animals were sacrificed immediately or four weeks later to measure progenitor proliferation or levels of neurogenesis. We also used a hippocampal-dependent task, the Morris water maze, to measure possible alterations in spatial memory. Moderate levels of voluntary running for nine days were found to significantly increase progenitor proliferation and neurogenesis by almost 500% compared to non-running rats. We found that these effects were regulated through endogenous opioids and that phosphorylated CREB was involved in the running induced effects. Four weeks after the cessation of moderate levels of voluntary running, large pool of new neurons was generated with improvements seen in spatial memory. In contrast, high levels of voluntary running for 24 days were found to decrease progenitor proliferation levels compared to non-running rats. In these animals, we found a concomitant increase in corticosterone levels, an increased adrenal gland size and a decreased thymus size, indicating high levels of a response to stress. These negative effects were prevented by restricting daily running distances to more moderate levels over the 24 days. Interestingly, un-restricted long-term running increased progenitor survival with a small increase in neurogenesis and no effects seen on spatial memory compared to non-running rats. Extended running for 43 days was found to normalise progenitor proliferation, despite indications of a chronic response to stress. In these rats, we found increased levels of brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in the hippocampus and frontal cortex, which may be an important part of a compensatory mechanism during periods of stress to maintain homeostasis in the brain. These findings demonstrate that moderate levels of voluntary running are most beneficial in promoting increased levels of neurogenesis in the brain and improving hippocampal function. There also exists an innate compensatory mechanism within the brain to attempt to restore homeostasis under periods of stress.
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